The effects of changes in the content of dietary carbohydrate, protein and fat on glucose metabolism and insulin secretion were examined in normal male rats. The animals were fed for 10 days with three types of diet: (a) standard diet, (b) glucose diet and (c) high fat/protein diet. The weight of the rats fed with the glucose diet decreased when compared to the standard diet fed rats. The glucose diet decreased insulin secretion in response to glucose in vivo and in vitro and slightly improved glucose tolerance. The hepatic glycogen content was approximately three times higher in animals fed with the glucose diet than in the control group. When compared to the standard diet, the high fat/protein diet induced an increase of the weight gain. This type of diet caused an increase of the fasting plasma glucose, a decrease of hepatic glycogen and a marked glucose intolerance to an intravenous load as demonstrated by lower rates of glucose disappearance. Plasma insulin levels were increased both in basal and glucose stimulated states. These results indicate that the glucose diet leads to an enhanced insulin sensitivity of the target tissues. By contrast, the high fat/protein diet induces an obesity-like state and an in vivo insulin resistance.